Automated Simultaneous Monitoring of the Conversion and Enantiomer Excess for the Enantiomeric Kinetic Resolution of Epichlorohydrin Using On-line Achiral Hplc with Coupled Uv and Polarimetric Detection

Traditionally, reaction conversion and enantiomeric excess (% ee) of products are monitored using two separate HPLC or GC systems, one system for monitoring the reaction conversion and the other system for determining the % ee. In addition, in-process samples are usually sampled manually, limiting the continuous monitoring of reaction process. For the first time, a fully automated on-line achiral HPLC system coupled with a laser polarimetric chiral detector was developed in this work to simultaneously monitor both the reaction conversion and % ee of the kinetic resolution for epichlorohydrin, which was selected as a model reaction to demonstrate the feasibility of the novel system. Both conversion and % ee of products were determined using a single HPLC analysis that did not require an expensive chiral column or tedious sample preparation steps. Excellent kinetic profiles were obtained for both reaction conversion and % ee. These kinetic data are crucial for process optimization, such as catalyst screening, solvent selection, reaction temperature, reaction concentration, etc. The on-line system increased sample throughput significantly by dramatically decreasing the time consuming and tedious analytical sample handling steps, which may interfere with the quality of the information determined. KEYWORD: ON-LINE HPLC, POLARIMETER, REACTION CONVERSION, ENANTIOMERIC EXCESS, HYDROLYTIC KINETIC RESOLUTION, EPICHLOROHYDRIN